General Information of Drug Off-Target (DOT) (ID: OT61924T)

DOT Name DnaJ homolog subfamily A member 3, mitochondrial (DNAJA3)
Synonyms DnaJ protein Tid-1; hTid-1; Hepatocellular carcinoma-associated antigen 57; Tumorous imaginal discs protein Tid56 homolog
Gene Name DNAJA3
Related Disease
Congenital myasthenic syndrome ( )
Alzheimer disease ( )
Breast cancer ( )
Breast carcinoma ( )
Breast neoplasm ( )
Colon cancer ( )
Colon carcinoma ( )
Colorectal neoplasm ( )
Dilated cardiomyopathy ( )
Dilated cardiomyopathy 1A ( )
Familial adenomatous polyposis ( )
Head-neck squamous cell carcinoma ( )
Metastatic malignant neoplasm ( )
Myocardial infarction ( )
Non-small-cell lung cancer ( )
Polyneuropathy ( )
Advanced cancer ( )
Complex neurodevelopmental disorder ( )
Glioma ( )
Neoplasm ( )
Schizophrenia ( )
UniProt ID
DNJA3_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
2CTT; 2DN9; 6IWS; 7X89
Pfam ID
PF00226 ; PF01556 ; PF00684
Sequence
MAARCSTRWLLVVVGTPRLPAISGRGARPPREGVVGAWLSRKLSVPAFASSLTSCGPRAL
LTLRPGVSLTGTKHNPFICTASFHTSAPLAKEDYYQILGVPRNASQKEIKKAYYQLAKKY
HPDTNKDDPKAKEKFSQLAEAYEVLSDEVKRKQYDAYGSAGFDPGASGSQHSYWKGGPTV
DPEELFRKIFGEFSSSSFGDFQTVFDQPQEYFMELTFNQAAKGVNKEFTVNIMDTCERCN
GKGNEPGTKVQHCHYCGGSGMETINTGPFVMRSTCRRCGGRGSIIISPCVVCRGAGQAKQ
KKRVMIPVPAGVEDGQTVRMPVGKREIFITFRVQKSPVFRRDGADIHSDLFISIAQALLG
GTARAQGLYETINVTIPPGTQTDQKIRMGGKGIPRINSYGYGDHYIHIKIRVPKRLTSRQ
QSLILSYAEDETDVEGTVNGVTLTSSGGSTMDSSAGSKARREAGEDEEGFLSKLKKMFTS
Function
Modulates apoptotic signal transduction or effector structures within the mitochondrial matrix. Affect cytochrome C release from the mitochondria and caspase 3 activation, but not caspase 8 activation. Isoform 1 increases apoptosis triggered by both TNF and the DNA-damaging agent mytomycin C; in sharp contrast, isoform 2 suppresses apoptosis. Can modulate IFN-gamma-mediated transcriptional activity. Isoform 2 may play a role in neuromuscular junction development as an effector of the MUSK signaling pathway.
Tissue Specificity Widely expressed with highest levels in heart, liver, lung and skeletal muscles. Also expressed in keratinocytes.
KEGG Pathway
Viral carcinogenesis (hsa05203 )

Molecular Interaction Atlas (MIA) of This DOT

21 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Congenital myasthenic syndrome DISJLG2T Definitive Biomarker [1]
Alzheimer disease DISF8S70 Strong Biomarker [2]
Breast cancer DIS7DPX1 Strong Altered Expression [3]
Breast carcinoma DIS2UE88 Strong Altered Expression [3]
Breast neoplasm DISNGJLM Strong Altered Expression [3]
Colon cancer DISVC52G Strong Altered Expression [4]
Colon carcinoma DISJYKUO Strong Altered Expression [4]
Colorectal neoplasm DISR1UCN Strong Altered Expression [4]
Dilated cardiomyopathy DISX608J Strong Biomarker [5]
Dilated cardiomyopathy 1A DIS0RK9Z Strong Biomarker [6]
Familial adenomatous polyposis DISW53RE Strong Genetic Variation [4]
Head-neck squamous cell carcinoma DISF7P24 Strong Biomarker [7]
Metastatic malignant neoplasm DIS86UK6 Strong Biomarker [3]
Myocardial infarction DIS655KI Strong Biomarker [6]
Non-small-cell lung cancer DIS5Y6R9 Strong Biomarker [8]
Polyneuropathy DISB9G3W Strong Biomarker [9]
Advanced cancer DISAT1Z9 moderate Biomarker [7]
Complex neurodevelopmental disorder DISB9AFI Limited Autosomal recessive [10]
Glioma DIS5RPEH Limited Biomarker [11]
Neoplasm DISZKGEW Limited Biomarker [7]
Schizophrenia DISSRV2N Limited Genetic Variation [12]
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⏷ Show the Full List of 21 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
17 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate increases the expression of DnaJ homolog subfamily A member 3, mitochondrial (DNAJA3). [13]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of DnaJ homolog subfamily A member 3, mitochondrial (DNAJA3). [14]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of DnaJ homolog subfamily A member 3, mitochondrial (DNAJA3). [15]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of DnaJ homolog subfamily A member 3, mitochondrial (DNAJA3). [16]
Estradiol DMUNTE3 Approved Estradiol increases the expression of DnaJ homolog subfamily A member 3, mitochondrial (DNAJA3). [17]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of DnaJ homolog subfamily A member 3, mitochondrial (DNAJA3). [18]
Carbamazepine DMZOLBI Approved Carbamazepine affects the expression of DnaJ homolog subfamily A member 3, mitochondrial (DNAJA3). [19]
Marinol DM70IK5 Approved Marinol decreases the expression of DnaJ homolog subfamily A member 3, mitochondrial (DNAJA3). [20]
Selenium DM25CGV Approved Selenium decreases the expression of DnaJ homolog subfamily A member 3, mitochondrial (DNAJA3). [21]
Isotretinoin DM4QTBN Approved Isotretinoin decreases the expression of DnaJ homolog subfamily A member 3, mitochondrial (DNAJA3). [22]
Diclofenac DMPIHLS Approved Diclofenac affects the expression of DnaJ homolog subfamily A member 3, mitochondrial (DNAJA3). [19]
Acocantherin DM7JT24 Approved Acocantherin increases the expression of DnaJ homolog subfamily A member 3, mitochondrial (DNAJA3). [23]
Urethane DM7NSI0 Phase 4 Urethane decreases the expression of DnaJ homolog subfamily A member 3, mitochondrial (DNAJA3). [24]
Tocopherol DMBIJZ6 Phase 2 Tocopherol decreases the expression of DnaJ homolog subfamily A member 3, mitochondrial (DNAJA3). [21]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 increases the expression of DnaJ homolog subfamily A member 3, mitochondrial (DNAJA3). [25]
THAPSIGARGIN DMDMQIE Preclinical THAPSIGARGIN increases the expression of DnaJ homolog subfamily A member 3, mitochondrial (DNAJA3). [26]
Bisphenol A DM2ZLD7 Investigative Bisphenol A affects the expression of DnaJ homolog subfamily A member 3, mitochondrial (DNAJA3). [27]
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⏷ Show the Full List of 17 Drug(s)

References

1 Mutations in MUSK causing congenital myasthenic syndrome impair MuSK-Dok-7 interaction. Hum Mol Genet. 2010 Jun 15;19(12):2370-9. doi: 10.1093/hmg/ddq110. Epub 2010 Apr 6.
2 Beta-Amyloid Increases the Expression Levels of Tid1 Responsible for Neuronal Cell Death and Amyloid Beta Production.Mol Neurobiol. 2020 Feb;57(2):1099-1114. doi: 10.1007/s12035-019-01807-2. Epub 2019 Nov 4.
3 Tid1 negatively regulates the migratory potential of cancer cells by inhibiting the production of interleukin-8.Cancer Res. 2005 Oct 1;65(19):8784-91. doi: 10.1158/0008-5472.CAN-04-4422.
4 Progression of colorectal cancers correlates with overexpression and loss of polarization of expression of the htid-1 tumor suppressor.Int J Mol Med. 2008 Jan;21(1):19-31.
5 A crucial role of mitochondrial Hsp40 in preventing dilated cardiomyopathy.Nat Med. 2006 Jan;12(1):128-32. doi: 10.1038/nm1327. Epub 2005 Dec 4.
6 Tumorous imaginal disc 1 (TID1) inhibits isoproterenol-induced cardiac hypertrophy and apoptosis by regulating c-terminus of hsc70-interacting protein (CHIP) mediated degradation of Gs.Int J Med Sci. 2018 Oct 20;15(13):1537-1546. doi: 10.7150/ijms.24296. eCollection 2018.
7 HSP40 co-chaperone protein Tid1 suppresses metastasis of head and neck cancer by inhibiting Galectin-7-TCF3-MMP9 axis signaling.Theranostics. 2018 Jun 13;8(14):3841-3855. doi: 10.7150/thno.25784. eCollection 2018.
8 Tid1-S regulates the mitochondrial localization of EGFR in non-small cell lung carcinoma.Oncogenesis. 2017 Jul 17;6(7):e361. doi: 10.1038/oncsis.2017.62.
9 A novel variant of the human mitochondrial DnaJ protein, Tid1, associates with a human disease exhibiting developmental delay and polyneuropathy.Eur J Hum Genet. 2019 Jul;27(7):1072-1080. doi: 10.1038/s41431-019-0358-9. Epub 2019 Feb 15.
10 Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
11 Identification of a hTid-1 mutation which sensitizes gliomas to apoptosis.FEBS Lett. 2004 Dec 17;578(3):323-30. doi: 10.1016/j.febslet.2004.11.034.
12 Genome-wide association study of schizophrenia in Ashkenazi Jews.Am J Med Genet B Neuropsychiatr Genet. 2015 Dec;168(8):649-59. doi: 10.1002/ajmg.b.32349. Epub 2015 Jul 21.
13 Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
14 Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
15 Increased mitochondrial ROS formation by acetaminophen in human hepatic cells is associated with gene expression changes suggesting disruption of the mitochondrial electron transport chain. Toxicol Lett. 2015 Apr 16;234(2):139-50.
16 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
17 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
18 Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
19 Drug-induced endoplasmic reticulum and oxidative stress responses independently sensitize toward TNF-mediated hepatotoxicity. Toxicol Sci. 2014 Jul;140(1):144-59. doi: 10.1093/toxsci/kfu072. Epub 2014 Apr 20.
20 THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
21 Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
22 Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
23 Ouabain impairs cell migration, and invasion and alters gene expression of human osteosarcoma U-2 OS cells. Environ Toxicol. 2017 Nov;32(11):2400-2413. doi: 10.1002/tox.22453. Epub 2017 Aug 10.
24 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
25 Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
26 Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
27 Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids in vitro and rat liver in vivo. Environ Res. 2019 Jun;173:124-134. doi: 10.1016/j.envres.2019.03.035. Epub 2019 Mar 18.